Dimethylformamide → HCID 71075900, compound

HRID 2283182Notes

Reaction equation

HRID 2283182 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.[Cl:11][C:12]1[C:13]([C:19]#[N:20])=[N:14][CH:15]=[C:16](Cl)[CH:17]=1.CN(C)C=O.CCCCCCC>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C([O-])([O-])=O.[K+].[K+].O>[Cl:1][C:2]1[CH:3]=[C:4]([C:16]2[CH:17]=[C:12]([Cl:11])[C:13]([C:19]#[N:20])=[N:14][CH:15]=2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8900HeptaneHCID 2734323(3-Chlorophenyl)boronic acidHCID 27696993,5-Dichloro-2-cyanopyridine

Product 1

HCID 71075900HCID 71075900, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 11430Potassium CarbonateCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

A 20 L reactor equipped with a mechanical stirrer, dip tube, thermometer and nitrogen inlet was charged with (3-chlorophenyl)boronic acid (550 g, 3.52 mol), 3,5-dichloro-2-cyanopyridine (639 g, 3.69 mol), K2CO3 (5.5 g, 40 mmol), [1,1′-bis(diphenyphosphino)ferrocene]dichloro-palladium(II) [PdCl2(dppf)] (11.5 g, 140 mmol), and dimethylformamide (3894 g, 4.125 L). The reaction solution was agitated and purged with nitrogen through the dip-tube for 30 minutes. Degassed water (413 g) was then charged to the reaction mixture while maintaining a temperature of less than 50° C. 25 hours. The reaction was determined to be complete due to the disappearance of 3,5-dichloro-2-cyanopyridine as measured by TLC analysis using ethyl acetate/methanol (4:1) as the mobile phase and UV 435 nm to visualize the reaction components. The reaction solution was then cooled to 5° C. and charged with heptane (940 g, 1.375 L) and agitated for 30 minutes. Water (5.5 L) was charged and the mixture was further agitated for 1 hour as the temperature was allowed to rise to 15° C. The solid product was isolated by filtration and washed with water (5.5 L) followed by heptane (18881 g, 2750 ML). The resulting cake was air dried under vacuum for 18 hours and then triturated with a mixture of 2-propanol (6908 g, 8800 mL0 and heptane (1 g, 2200 mL0 at 50° C. for 4 hours, cooled to ambient temperature and then agitated at ambient temperature for 1 hour. The product was then isolated by filtration and washed with cold 2-propanol (3450 g, 4395 mL) followed by heptane (3010 g, 4400 mL). The resulting solid was dried under high vacuum at 40° C. for 64 hours to afford 565.9 g (65% yield) of the desired product as a beige solid. Purity by HPLC was 98.3. 1H NMR (DMSO-d6) δ 9.12 (d, 1H), 8.70 (d, 1H), 8.03 (t, 1H) 7.88 (m, 1H), and 7.58 (m, 2H).

Workup

  1. customA 20 L reactor equipped with a mechanical stirrer, dip tube
  2. custompurged with nitrogen through the dip-tube for 30 minutes
  3. additionDegassed water (413 g) was then charged to the reaction mixture
  4. temperaturewhile maintaining a temperature of less than 50° C
  5. custom25 hours
  6. customthe reaction components
  7. stirringagitated for 30 minutes
  8. stirringthe mixture was further agitated for 1 hour as the temperature
  9. customto rise to 15° C
  10. customThe solid product was isolated by filtration
  11. washwashed with water (5.5 L)
  12. customdried under vacuum for 18 hours
  13. customtriturated with a mixture of 2-propanol (6908 g, 8800 mL0 and heptane (1 g, 2200 mL0 at 50° C. for 4 hours
  14. temperaturecooled to ambient temperature
  15. stirringagitated at ambient temperature for 1 hour
  16. customThe product was then isolated by filtration
  17. washwashed with cold 2-propanol (3450 g, 4395 mL)
  18. customThe resulting solid was dried under high vacuum at 40° C. for 64 hours

Sources & evidence

ORD record
ord-9b50b5fb46aa4630abc1b574f38f0c00
Source dataset
uspto-grants-2015_09
Patent number
US09145366B2

Reaction notes

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